In a previous study, treatment of rats with 10% glucose in the drinking water, as fetuses during gestation and for 1.5 months after delivery, significantly enhanced tumor incidence that resulted from N-methyl-N-nitrosourea (MNU, 20 mg/kg) given transplacentally on gestation day 21, with a 1.6-fold increase in overall tumor incidence. We investigated whether glucose would have an effect on MNU-induced mutation in fetal F-344 rat somatic cells as measured in an in vivo/in vitro assay. Rat fetuses were exposed transplacentally to MNU on gestation day 16 and to a 10% glucose solution from gestation day 7 to day 17. Cells were isolated on gestation day 17 for determination of cloning efficiency and for selection of 6-thioguanine (6-TG)-resistant HGPRT mutants. Cloning efficiency of the fetal cells exposed to MNU alone was 22.6+/-2.3% S.E., while that for cells from fetuses exposed to MNU+glucose was 27.5+/-1.6% S.E., which was a significant difference (P=0.018). This indicates an effect of glucose on cell proliferation and survival. MNU treatment significantly increased the mutation frequency of fetal cells from a spontaneous value of 0.4 x 10(-6) per viable cell to (8.8+/-1.8 S.E.,) x 10(-6) (P=0.0087). The coexposure to MNU and glucose yielded a mutant frequency per plate of 0.62+/-0.05 S.E., which was a 1.5-fold increase compared to MNU alone (0.43+/-0.11 S.E., P=0.075. In summary, the data indicate that glucose during pregnancy increases proliferation/survival of fetal cells and possibly also mutation rate.